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Proteins kinase Cɛ is required for non-small cell lung carcinoma growth and regulates the expression of apoptotic genes.

Authors :
Caino MC
Lopez-Haber C
Kim J
Mochly-Rosen D
Kazanietz MG
Source :
Oncogene [Oncogene] 2012 May 17; Vol. 31 (20), pp. 2593-600. Date of Electronic Publication: 2011 Sep 26.
Publication Year :
2012

Abstract

Protein kinase C (PKC)ɛ, a member of the novel PKC family, has key roles in mitogenesis and survival in normal and cancer cells. PKCɛ is frequently overexpressed in epithelial cancers, particularly in lung cancer. Using a short-hairpin RNA approach, here we established that PKCɛ is required for non-small cell lung carcinoma (NSCLC) growth in vitro as well as tumor growth when inoculated into athymic mice. Moreover, sustained delivery of a PKCɛ-selective inhibitor peptide, ɛV1-2, reduced xenograft growth in mice. Both RNA interference depletion and pharmacological inhibition of PKCɛ caused a marked elevation in the number of apoptotic cells in NSCLC tumors. PKCɛ-depleted NSCLC cells show elevated expression of pro-apoptotic proteins of the Bcl-2 family, caspase recruitment domain-containing proteins and tumor necrosis factor ligands/receptor superfamily members. Moreover, a Gene Set Enrichment Analysis revealed that a vast majority of the genes changed in PKCɛ-depleted cells were also deregulated in human NSCLC. Our results strongly suggest that PKCɛ is required for NSCLC cell survival and maintenance of NSCLC tumor growth. Therefore, PKCɛ may represent an attractive therapeutic target for NSCLC.

Details

Language :
English
ISSN :
1476-5594
Volume :
31
Issue :
20
Database :
MEDLINE
Journal :
Oncogene
Publication Type :
Academic Journal
Accession number :
21996750
Full Text :
https://doi.org/10.1038/onc.2011.428